Marfan’s syndrome

Published on 05/05/2015 by admin

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Last modified 22/04/2025

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226 Marfan’s syndrome

Instruction

Look at this patient.

Examine this patient’s heart.

Salient features

History

• Family history.

Examination

• Disproportionately long limbs compared with the trunk: the arm span will exceed the height.

Proceed by examining:

• hands for hypermobile joints and spidery fingers or arachnodactyly; confirmed by:

• thumb sign (Steinberg test; Fig. 226.1): asking the patient to clench his thumb in his fist; the thumb should not exceed beyond the ulnar side of the hand in normal subjects but because of hypermobility and laxity of the joint in Marfan’s disease the entire thumbnail projects beyond the border of the hand

• wrist sign (Walker–Murdoch sign; Fig. 226.2): when the wrist is grasped by the contralateral hand, the thumb overlaps the terminal phalanx of the fifth digit by at least 1 cm in 80% of patients (Arch Intern Med 1970;126:276).

• eyes, for iridodonesis or ectopia lentis (subluxation upwards): the patient may be wearing thick spectacles; blue sclera

• head, for long-headedness: dolichocephalic with bossing of frontal eminences and prominent supraorbital ridges

• palate for high arched palate

• skin for small papules in the neck (Miescher’s elastoma)

• chest for pectus excavatum, cystic lung disease (Thorax 1984;39:780–4)

• heart for mitral valve prolapse, aortic aneurysm and aortic regurgitation

• spine for scoliosis and kyphosis.

Fig. 226.1 Steinberg test or thumb sign.

Fig. 226.2 The Walker Murdoch test or wrist sign.

Remember: Every patient should be referred for ophthalmic examination, annual echocardiography and genetic counselling to maximize the preventive potential in this disease.

Diagnosis

This patient has Marfan syndrome and aortic regurgitation (lesion) and is limited by cardiac failure (functional status).

Questions

What are the criteria for Marfan syndrome?

• People with no family history require, apart from skeletal features (including pectus carinatum or excavatum, reduced upper-to-lower segment ratio, arm-span-to-height ratio >1.05, scoliosis and reduced elbow extension), involvement of at least two other systems and one of the major criteria (these include ectopia lentis, dilatation of the aortic root or aortic dissection and lumbosacral dural ectasia by CT or MRI).

• Patients with a family history need features in at least two systems.

What is your differential diagnosis?

Homocystinuria (recessively inherited inborn error of amino acid metabolism caused by a deficiency of cystathionine β-synthetase) in which the skeletal features are similar.

How would you differentiate homocystinuria and Marfan syndrome?

In homocystinuria, the lens is dislocated downwards and there is homocystine in the urine.

Advanced-level questions

Why do these patients need annual echocardiography?

To monitor aortic diameter and mitral valve function. Prophylactic replacement of the aortic root with a composite graft when the diameter reaches 50–55 mm (normal <40 mm) prolongs life. Untreated patients commonly die in the fourth or fifth decade from dissection of the aorta or from cardiac failure caused by aortic regurgitation. Chronic beta-blockade to produce a negative inotropic effect retards the rate of aortic dilatation (N Engl J Med 1994;330:1335–41). Also, patients should be advised regarding infective endocarditis prophylaxis.

What is the common cause of mortality in Marfan syndrome?

Cardiovascular complications cause 95% of deaths in such patients and reduce mean life expectancy by 40%.

What are the ocular features of Marfan syndrome?

• Subluxation of lens

• Small and spherical lens

• Hypoplasia of dilator pupillae, making pupillary dilatation difficult

• Flat cornea

• Retinal detachment.

What are the complications of pregnancy in women with Marfan syndrome?

• Early premature abortion

• Risk of maternal death from aortic dissection. Pregnancy is not dangerous when the aortic diameter is <40 mm.

Is there a gene implicated in Marfan syndrome?

Marfan syndrome appears to be caused by mutations in a single gene FBN1 on chromosome 15 and encoding fibrillin (N Engl J Med 1992;326:905, Genomics 1993;17:468–75). Fibrillin is a glycoprotein produced by fibroblasts that aggregates alone or with other proteins in the extracellular matrix to form microfibrillary fibres on which elastin can be deposited. These fibres are particularly abundant in the ciliary zonules that support the lens, in ligaments and in the aorta. Dilatation of the aorta occurs as a result of cystic medionecrosis.

One study has suggested that the angiotensin II type 1 receptor antagonist losartan antagonizes the action of transforming growth factor-β in preventing aortic dilatation in mice with mutant fibrillin-1. Therapy for 6 months stopped progression of aortic dilatation and elastin fragmentation in the aortic wall, a histologic hallmark of Marfan syndrome. A beta-blocker, currently the therapy of choice for Marfan syndrome, was also effective but not as effective as losartan. In a small cohort study (n = 18), the use of an angiotensin II receptor antagonist in patients with Marfan syndrome significantly slowed the rate of progressive aortic root dilation (N Engl J Med 2008;358:2787). Another small study reported that perindopril reduced both aortic stiffness and aortic root diameter in patients with Marfan syndrome (JAMA 2007;298:1539–47). The US National Institutes of Health is sponsoring a clinical trial that will compare losartan with beta-blocker therapy in children and young adults with Marfan syndrome and aortic aneurysm.

American President Abraham Lincoln is suspected to have had Marfan syndrome.

B-J Antoine Marfan (1858–1942), a French paediatrician, wrote his paper in 1896. He was appointed Foundation Professor of Hygiene at the Clinic of Infantile Diseases in Paris in 1914. He was elected honorary fellow of the Royal Society of Medicine, UK in 1934.

Victor McKusick, contemporary Professor of Medicine at Johns Hopkins Hospital, Baltimore, whose chief interest is genetics.

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